Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.0
6.0
Journals
Cells
Special Issues
Chimeric Antigen Receptor T-Cell Therapy
share announcement

Chimeric Antigen Receptor T-Cell Therapy

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (30 April 2020) | Viewed by 48678

Special Issue Editor

Prof. Dr. Michael Schmitt

E-Mail Website
Guest Editor
1. Department of Internal Medicine V, University Hospital Heidelberg, 69120 Heidelberg, Germany
2. German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT), German Cancer Consortium (DKTK), 69120 Heidelberg, Germany
Interests: tumor antigens; peptide vacation; cell therapy; CAR T cells; TCR T cells; tolerance induction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

CAR T cell therapy with two commercial products recently came into clinical practice both in the US and Europe. Hematologists and oncologist are getting more and more familiar with the potential of CAR T cell therapy, its effectiveness, and side effects.

Clinical practice taught us that therapy is safe when physicians and nurses are well-prepared and instructed in the classification of side effects as well as in therapeutic algorithms. The clinical effectiveness of CAR T cells depends on tumor size, number and functionality of cells, and the therapy line in which CAR T cell therapy is employed.

Every day, we are discovering new aspects of CAR T cell therapy and that we need new tools and algorithms to make CAR T cell therapy more effective. Additionally, the entire process is translational: Clinicians have to learn from researchers and vice versa. That sparks new excitement and enthusiasm.

The aim of this Special Issue is to address preclinical, translational, and clinical aspects of current CAR T cell therapy for researchers and clinicians working in the field.

Therefore, I cordially invite you to submit preclinical, translational, and clinical work to this Special Issue.

Prof. Dr. Michael Schmitt
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • CAR vectors (2nd, 3rd, 4th generation/TRUCKs, armored CAR T cells, )
  • novel target antigens
  • clinical CAR T cell trials
  • side effects (CRS, ICANS)
  • NK CARs

Published Papers (6 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

17 pages, 2247 KiB  
Article
Current Challenges in Providing Good Leukapheresis Products for Manufacturing of CAR-T Cells for Patients with Relapsed/Refractory NHL or ALL
by Felix Korell, Sascha Laier, Sandra Sauer, Kaya Veelken, Hannah Hennemann, Maria-Luisa Schubert, Tim Sauer, Petra Pavel, Carsten Mueller-Tidow, Peter Dreger, Michael Schmitt and Anita Schmitt
Cells 2020, 9(5), 1225; https://doi.org/10.3390/cells9051225 - 15 May 2020
Cited by 38 | Viewed by 6786
Abstract
Background: T lymphocyte collection through leukapheresis is an essential step for chimeric antigen receptor T (CAR-T) cell therapy. Timing of apheresis is challenging in heavily pretreated patients who suffer from rapid progressive disease and receive T cell impairing medication. Methods: A total of [...] Read more.
Background: T lymphocyte collection through leukapheresis is an essential step for chimeric antigen receptor T (CAR-T) cell therapy. Timing of apheresis is challenging in heavily pretreated patients who suffer from rapid progressive disease and receive T cell impairing medication. Methods: A total of 75 unstimulated leukaphereses were analyzed including 45 aphereses in patients and 30 in healthy donors. Thereof, 41 adult patients with Non-Hodgkin’s lymphoma (85%) or acute lymphoblastic leukemia (15%) underwent leukapheresis for CAR-T cell production. Results: Sufficient lymphocytes were harvested from all patients even from those with low peripheral lymphocyte counts of 0.18/nL. Only four patients required a second leukapheresis session. Leukapheresis products contained a median of 98 × 108 (9 - 341 × 108) total nucleated cells (TNC) with 38 × 108 (4 - 232 × 108) CD3+ T cells. Leukapheresis products from healthy donors as well as from patients in complete remission were characterized by high TNC and CD3+ T lymphocyte counts. CAR-T cell products could be manufactured for all but one patient. Conclusions: Sufficient yield of lymphocytes for CAR-T cell production is feasible also for patients with low peripheral blood counts. Up to 12–15 L blood volume should be processed in patients with absolute lymphocyte counts ≤ 1.0/nL. Full article
(This article belongs to the Special Issue Chimeric Antigen Receptor T-Cell Therapy)
►▼ Show Figures

Figure 1

17 pages, 3553 KiB  
Article
Hinge and Transmembrane Domains of Chimeric Antigen Receptor Regulate Receptor Expression and Signaling Threshold
by Kento Fujiwara, Ayaka Tsunei, Hotaka Kusabuka, Erika Ogaki, Masashi Tachibana and Naoki Okada
Cells 2020, 9(5), 1182; https://doi.org/10.3390/cells9051182 - 9 May 2020
Cited by 77 | Viewed by 9968
Abstract
Chimeric antigen receptor (CAR)-T cells have demonstrated significant clinical potential; however, their strong antitumor activity may cause severe adverse effects. To ensure efficacy and safe CAR-T cell therapy, it is important to understand CAR’s structure–activity relationship. To clarify the role of hinge and [...] Read more.
Chimeric antigen receptor (CAR)-T cells have demonstrated significant clinical potential; however, their strong antitumor activity may cause severe adverse effects. To ensure efficacy and safe CAR-T cell therapy, it is important to understand CAR’s structure–activity relationship. To clarify the role of hinge and transmembrane domains in CAR and CAR-T cell function, we generated different chimeras and analyzed their expression levels and antigen-specific activity on CAR-T cells. First, we created a basic CAR with hinge, transmembrane, and signal transduction domains derived from CD3ζ, then we generated six CAR variants whose hinge or hinge/transmembrane domains originated from CD4, CD8α, and CD28. CAR expression level and stability on the T cell were greatly affected by transmembrane rather than hinge domain. Antigen-specific functions of most CAR-T cells depended on their CAR expression levels. However, CARs with a CD8α- or CD28-derived hinge domain showed significant differences in CAR-T cell function, despite their equal expression levels. These results suggest that CAR signaling intensity into T cells was affected not only by CAR expression level, but also by the hinge domain. Our discoveries indicate that the hinge domain regulates the CAR signaling threshold and the transmembrane domain regulates the amount of CAR signaling via control of CAR expression level. Full article
(This article belongs to the Special Issue Chimeric Antigen Receptor T-Cell Therapy)
►▼ Show Figures

Figure 1

15 pages, 2713 KiB  
Article
IL7-IL12 Engineered Mesenchymal Stem Cells (MSCs) Improve A CAR T Cell Attack Against Colorectal Cancer Cells
by Andreas A. Hombach, Ulf Geumann, Christine Günther, Felix G. Hermann and Hinrich Abken
Cells 2020, 9(4), 873; https://doi.org/10.3390/cells9040873 - 3 Apr 2020
Cited by 64 | Viewed by 5745
Abstract
Chimeric antigen receptor (CAR) redirected T cells are efficacious in the treatment of leukemia/lymphoma, however, showed less capacities in eliminating solid tumors which is thought to be partly due to the lack of cytokine support in the tumor lesion. In order to deliver [...] Read more.
Chimeric antigen receptor (CAR) redirected T cells are efficacious in the treatment of leukemia/lymphoma, however, showed less capacities in eliminating solid tumors which is thought to be partly due to the lack of cytokine support in the tumor lesion. In order to deliver supportive cytokines, we took advantage of the inherent ability of mesenchymal stem cells (MSCs) to actively migrate to tumor sites and engineered MSCs to release both IL7 and IL12 to promote homeostatic expansion and Th1 polarization. There is a mutual interaction between engineered MSCs and CAR T cells; in presence of CAR T cell released IFN-γ and TNF-α, chronic inflammatory Th2 MSCs shifted towards a Th17/Th1 pattern with IL2 and IL15 release that mutually activated CAR T cells with extended persistence, amplification, killing and protection from activation induced cell death. MSCs releasing IL7 and IL12 were superior over non-modified MSCs in supporting the CAR T cell response and improved the anti-tumor attack in a transplant tumor model. Data demonstrate the first use of genetically modified MSCs as vehicles to deliver immuno-modulatory proteins to the tumor tissue in order to improve the efficacy of CAR T cells in the treatment of solid malignancies. Full article
(This article belongs to the Special Issue Chimeric Antigen Receptor T-Cell Therapy)
►▼ Show Figures

Figure 1

Review

Jump to: Research

18 pages, 1185 KiB  
Review
Transposon-Based CAR T Cells in Acute Leukemias: Where Are We Going?
by Chiara F. Magnani, Sarah Tettamanti, Gaia Alberti, Ilaria Pisani, Andrea Biondi, Marta Serafini and Giuseppe Gaipa
Cells 2020, 9(6), 1337; https://doi.org/10.3390/cells9061337 - 27 May 2020
Cited by 29 | Viewed by 9092
Abstract
Chimeric Antigen Receptor (CAR) T-cell therapy has become a new therapeutic reality for refractory and relapsed leukemia patients and is also emerging as a potential therapeutic option in solid tumors. Viral vector-based CAR T-cells initially drove these successful efforts; however, high costs and [...] Read more.
Chimeric Antigen Receptor (CAR) T-cell therapy has become a new therapeutic reality for refractory and relapsed leukemia patients and is also emerging as a potential therapeutic option in solid tumors. Viral vector-based CAR T-cells initially drove these successful efforts; however, high costs and cumbersome manufacturing processes have limited the widespread clinical implementation of CAR T-cell therapy. Here we will discuss the state of the art of the transposon-based gene transfer and its application in CAR T immunotherapy, specifically focusing on the Sleeping Beauty (SB) transposon system, as a valid cost-effective and safe option as compared to the viral vector-based systems. A general overview of SB transposon system applications will be provided, with an update of major developments, current clinical trials achievements and future perspectives exploiting SB for CAR T-cell engineering. After the first clinical successes achieved in the context of B-cell neoplasms, we are now facing a new era and it is paramount to advance gene transfer technology to fully exploit the potential of CAR T-cells towards next-generation immunotherapy. Full article
(This article belongs to the Special Issue Chimeric Antigen Receptor T-Cell Therapy)
►▼ Show Figures

Figure 1

21 pages, 843 KiB  
Review
Paving the Way toward Successful Multiple Myeloma Treatment: Chimeric Antigen Receptor T-Cell Therapy
by Ewelina Grywalska, Barbara Sosnowska-Pasiarska, Jolanta Smok-Kalwat, Marcin Pasiarski, Paulina Niedźwiedzka-Rystwej and Jacek Roliński
Cells 2020, 9(4), 983; https://doi.org/10.3390/cells9040983 - 16 Apr 2020
Cited by 10 | Viewed by 4427
Abstract
Despite the significant progress of modern anticancer therapies, multiple myeloma (MM) is still incurable for the majority of patients. Following almost three decades of development, chimeric antigen receptor (CAR) T-cell therapy now has the opportunity to revolutionize the treatment landscape and meet the [...] Read more.
Despite the significant progress of modern anticancer therapies, multiple myeloma (MM) is still incurable for the majority of patients. Following almost three decades of development, chimeric antigen receptor (CAR) T-cell therapy now has the opportunity to revolutionize the treatment landscape and meet the unmet clinical need. However, there are still several major hurdles to overcome. Here we discuss the recent advances of CAR T-cell therapy for MM with an emphasis on future directions and possible risks. Currently, CAR T-cell therapy for MM is at the first stage of clinical studies, and most studies have focused on CAR T cells targeting B cell maturation antigen (BCMA), but other antigens such as cluster of differentiation 138 (CD138, syndecan-1) are also being evaluated. Although this therapy is associated with side effects, such as cytokine release syndrome and neurotoxicity, and relapses have been observed, the benefit–risk balance and huge potential drive the ongoing clinical progress. To fulfill the promise of recent clinical trial success and maximize the potential of CAR T, future efforts should focus on the reduction of side effects, novel targeted antigens, combinatorial uses of different types of CAR T, and development of CAR T cells targeting more than one antigen. Full article
(This article belongs to the Special Issue Chimeric Antigen Receptor T-Cell Therapy)
►▼ Show Figures

Figure 1

22 pages, 2159 KiB  
Review
MLL-Rearranged Acute Leukemia with t(4;11)(q21;q23)—Current Treatment Options. Is There a Role for CAR-T Cell Therapy?
by Oliver Britten, Denise Ragusa, Sabrina Tosi and Yasser Mostafa Kamel
Cells 2019, 8(11), 1341; https://doi.org/10.3390/cells8111341 - 29 Oct 2019
Cited by 47 | Viewed by 11908
Abstract
The MLL (mixed-lineage leukemia) gene, located on chromosome 11q23, is involved in chromosomal translocations in a subtype of acute leukemia, which represents approximately 10% of acute lymphoblastic leukemia and 2.8% of acute myeloid leukemia cases. These translocations form fusions with various [...] Read more.
The MLL (mixed-lineage leukemia) gene, located on chromosome 11q23, is involved in chromosomal translocations in a subtype of acute leukemia, which represents approximately 10% of acute lymphoblastic leukemia and 2.8% of acute myeloid leukemia cases. These translocations form fusions with various genes, of which more than 80 partner genes for MLL have been identified. The most recurrent fusion partner in MLL rearrangements (MLL-r) is AF4, mapping at chromosome 4q21, accounting for approximately 36% of MLL-r leukemia and particularly prevalent in MLL-r acute lymphoblastic leukemia (ALL) cases (57%). MLL-r leukemia is associated with a sudden onset, aggressive progression, and notoriously poor prognosis in comparison to non-MLL-r leukemias. Despite modern chemotherapeutic interventions and the use of hematopoietic stem cell transplantations, infants, children, and adults with MLL-r leukemia generally have poor prognosis and response to these treatments. Based on the frequency of patients who relapse, do not achieve complete remission, or have brief event-free survival, there is a clear clinical need for a new effective therapy. In this review, we outline the current therapy options for MLL-r patients and the potential application of CAR-T therapy. Full article
(This article belongs to the Special Issue Chimeric Antigen Receptor T-Cell Therapy)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-6
Back to TopTop